Promoting Compliance When Faith Gets in the Way.
Sixty-six percent of U.S. Christians report they believe God can heal supernaturally, 68% have prayed for someone to be healed supernaturally by God, and 27% state they have experienced a miraculous physical healing. Christians who hold such beliefs may struggle with seeking and adhering to a prescribed healthcare regimen, as well as experience shame. A health education seminar assisting congregants to view healthcare as compatible with faith was implemented and evaluated in a Christian faith community.


Overexpression of ankyrin repeat domain 1 enhances cardiomyocyte apoptosis by promoting p53 activation and mitochondrial dysfunction in rodents.
The Ankrd1 (ankyrin repeat domain 1) gene is known to be up-regulated in heart failure and acts as a co-activator of p53, modulating its transcriptional activity, but it remains inconclusive whether this gene promotes or inhibits cell apoptosis. In the present study, we attempted to investigate the role of Ankrd1 on AngII (angiotensin II)- or pressure-overload-induced cardiomyocyte apoptosis. In the failing hearts of mice with pressure overload, the protein expression of Ankrd1-encoded CARP (cardiac ankyrin repeat protein) was significantly increased. In NRCs (neonatal rat cardiomyocytes), AngII increased the expression of Ankrd1 and CARP. In the presence of AngII in NRCs, infection with a recombinant adenovirus containing rat Ankrd1 cDNA (Ad-Ankrd1) enhanced the mitochondrial translocation of Bax and phosphorylated p53, increased mitochondrial permeability and cardiomyocyte apoptosis, and reduced cell viability, whereas these effects were antagonized by silencing of Ankrd1. Intra-myocardial injection of Ad-Ankrd1 in mice with TAC (transverse aortic constriction) markedly exacerbated cardiac dysfunction with an increase in the lung weight/body weight ratio and a decrease in left ventricular fractional shortening. Cardiomyocyte apoptosis and the expression of phosphorylated p53 were also significantly increased in Ad-Ankrd1-infected TAC mice, whereas knockdown of Ankrd1 significantly inhibited the apoptotic signal pathway as well as cardiomyocyte apoptosis in pressure-overload mice. These findings indicate that overexpression of Ankrd1 exacerbates pathological cardiac dysfunction through enhancement of cardiomyocyte apoptosis mediated by the up-regulation of p53.


LAPTM4B-35 protein is a weak tumor-associated antigen candidate.
Lysosome-associated protein transmembrane 4β (LAPTM4B) is a gene that has been indicated to be involved in cancer. It is located at chromosome 8q22 and is composed of seven exons and six introns. LAPTM4B encodes two protein isoforms: LAPTM4B-35 and LAPTM4B-24. LAPTM4B-35 is markedly upregulated and LAPTM4B-24 is downregulated in several types of cancer. LAPTM4B-35 is 91 amino acids (N91) longer than LAPTM4B-24 at the N-terminus. In the present study, western blotting, enzyme-linked immunosorbent spot analysis and the B16F10-N91 tumor bearing-mice experiments were used to evaluate whether the overexpression of N91 indicates its potential as a candidate tumor-associated antigen. The results revealed that N91 was expressed in a wide range of normal mouse tissues and human peripheral blood mononuclear cells, with varying expression levels. The weak immunogenicity of N91 protein suggested it was a weak candidate antigen; however, the N91 protein was associated with cell proliferation.


Elav-Mediated Exon Skipping and Alternative Polyadenylation of the Dscam1 Gene Are Required for Axon Outgrowth.
Many metazoan genes express alternative long 3' UTR isoforms in the nervous system, but their functions remain largely unclear. In Drosophila melanogaster, the Dscam1 gene generates short and long (Dscam1-L) 3' UTR isoforms because of alternative polyadenylation (APA). Here, we found that the RNA-binding protein Embryonic Lethal Abnormal Visual System (Elav) impacts Dscam1 biogenesis at two levels, including regulation of long 3' UTR biogenesis and skipping of an upstream exon (exon 19). MinION long-read sequencing confirmed the connectivity of this alternative splicing event to the long 3' UTR. Knockdown or CRISPR deletion of Dscam1-L impaired axon outgrowth in Drosophila. The Dscam1 long 3' UTR was found to be required for correct Elav-mediated skipping of exon 19. Elav thus co-regulates APA and alternative splicing to generate specific Dscam1 transcripts that are essential for neural development. This coupling of APA to alternative splicing might represent a new class of regulated RNA processing.


Contrast echocardiography in the diagnosis of intrapulmonary vascular dilations in candidates for liver transplantation.
To determine the importance of contrast echocardiography in the diagnosis of intrapulmonary vascular dilations in patients with severe liver disease, who are candidates for liver transplantation. The study comprised 76 patients with chronic liver disease and no evidence of intrinsic pulmonary disease, heart failure, or congenital heart disease with intracardiac communications, who underwent transthoracic echocardiography with second harmonic imaging. Thirty-two of them underwent consecutive transesophageal study. The result of contrast echocardiography was considered positive when the presence of contrast was detected in the left cardiac chambers with a delay of 4 to 6 cardiac cycles after initial opacification of the right cardiac chambers. The prevalence of intrapulmonary vascular dilations was 53.9% (41/76 patients). The sensitivity, specificity, positive and negative predictive values, and accuracy of transthoracic echocardiography as compared with those of transesophageal echocardiography for confirming pulmonary vascular abnormalities in patients with liver disease were, respectively, 75%, 100%, 100%, 80%, and 87.5%. The degree of arterial oxygenation showed no correlation with the occurrence of a positive echocardiographic study. Arterial hypoxemia (PaO2 < 70 mm Hg) was observed in 9 (15.9%) of the 76 patients. The echocardiographic study was positive in 37 (55.2%) of the 67 nonhypoxemic patients and in 4 (44.4%) of the 9 hypoxemic ones. Contrast echocardiography proved to be effective, easy, and safe to use in candidates for liver transplantation. Transthoracic echocardiography may be used in the diagnostic routine of intrapulmonary vascular dilations, the transesophageal study being reserved for inconclusive cases with clinical suspicion.


Comprehensive Characterization of Transforming Growth Factor Beta Receptor 1 in Stomach Adenocarcinoma Identifies a Prognostic Signature for Predicting Clinical Outcomes and Immune Infiltrates.
Stomach adenocarcinoma (STAD) ranks as the third leading cause of cancer death worldwide. TGF‑β receptor 1 (TGFBR1), serving important roles in the TGF‑β family, the mechanisms whereby TGFBR1 governs tumor progression, immune cell infiltration in STAD remains unintelligible. We used the TCGA, GEPIA, and HPA databases to explore TGFBR1 expression in STAD, the correlation between TGFBR1 expression and the clinical features. A receiver operating characteristic (ROC) curve and nomogram were constructed, and LASSO (the Least Absolute Shrinkage and Selection Operator)-selected features were used to build the TGFBR1 prognostic signature. GSEA is used to find the potential mechanism of TGFBR1 to promote the malignant process of STAD. We explored the influence of the TGFBR1 on the immune microenvironment of STAD through the TIMER2.0 and GEPIA database. In our study, TGFBR1 expression was significantly elevated in STAD and positively co-expression with pathologic stage, lymph node metastases (LNM) stage and histopathological grade. Nine factors with non-zero coefficients were identified by LASSO-selected features. Survival analysis revealed that patients with high TGFBR1 had shorter OS, FP, and PPS. Multivariate Cox analysis revealed that TGFBR1 was an independent prognostic factor for OS in STAD. The ROC analysis suggested that high diagnostic value with the AUC of TGFBR1 was 0.739. GSEA revealed that high TGFBR1 expression was correlated with pathway in cancer, MAPK signaling pathway, NOTCH signaling pathway, and VEGF-C production. ssGSEA showed that TGFBR1 is correlated with NK cells, Tem and Th17 cells. Furthermore, elevated TGFBR1 expression was found to be significantly correlated with several immune checkpoint and immune markers associated with immune cell subsets. In summary, TGFBR1 could be a prognostic biomarker and an important regulator of immune cell infiltration in STAD. The present study revealed the probable underlying molecular mechanisms of TGFBR1 in STAD and provided a potential target for improving the prognosis.


Mission statements and vision documents in medical practices.
Thoughtful, carefully constructed mission statements and vision documents serve both to signal the purpose of a medical practice to the public and other professional colleagues, and to keep the practice's providers focused on its key purposes. Practice culture is the primary driver ofmission and vision. We clarify the differences between mission statements and vision documents, and offer guidelines to aid in constructing them.


Association between lactate/albumin ratio and all-cause mortality in patients with acute respiratory failure: A retrospective analysis.
Previous studies have shown that lactate/albumin ratio (LAR) can be used as a prognostic biomarker to independently predict the mortality of sepsis and severe heart failure. However, the role of LAR as an independent prognostic factor in all-cause mortality in patients with acute respiratory failure (ARF) remains to be clarified. Therefore, we retrospectively analyzed 2170 patients with ARF in Medical Information Mart for Intensive Care Database III from 2001 to 2012. By drawing the receiver operating characteristic curve, LAR shows a better predictive value in predicting the 30-day mortality of ARF patients (AUC: 0.646), which is higher than that of albumin (AUC: 0.631) or lactate (AUC: 0.616) alone, and even higher than SOFA score(AUC: 0.642). COX regression analysis and Kaplan-Meier curve objectively and intuitively show that high LAR is a risk factor for patients with ARF, which is positively correlated with all-cause mortality. As an easy-to-obtain and objective biomarker, LAR deserves further verification by multi-center prospective studies.


Peptidoglycans promotes human leukemic THP-1 cell apoptosis and differentiation.
The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll- like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-1β, interleukin-8 and TNF-α and apoptosis of THP-1 with PGN dose and time dependence. Moreover , in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-α-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.


Microwave-Assisted Hydrothermal Rapid Synthesis of Calcium Phosphates: Structural Control and Application in Protein Adsorption.
Synthetic calcium phosphate (CaP)-based materials have attracted much attention in the biomedical field. In this study, we have investigated the effect of pH values on CaP nanostructures prepared using a microwave-assisted hydrothermal method. The hierarchical nanosheet-assembled hydroxyapatite (HAP) nanostructure was prepared under weak acidic conditions (pH 5), while the HAP nanorod was prepared under neutral (pH 7) and weak alkali (pH 9) condition. However, when the pH value increases to 11, a mixed product of HAP nanorod and tri-calcium phosphate nanoparticle was obtained. The results indicated that the pH value of the initial reaction solution played an important role in the phase and structure of the CaP. Furthermore, the protein adsorption and release performance of the as-prepared CaP nanostructures were investigated by using hemoglobin (Hb) as a model protein. The sample that was prepared at pH = 11 and consisted of mixed morphologies of nanorods and nanoprisms showed a higher Hb protein adsorption capacity than the sample prepared at pH 5, which could be explained by its smaller size and dispersed structure. The results revealed the relatively high protein adsorption capacity of the as-prepared CaP nanostructures, which show promise for applications in various biomedical fields such as drug delivery and protein adsorption.


Validated polarographic methods for the determination of certain antibacterial drugs.
Two simple, precise, inexpensive and sensitive voltammetric methods for the determination of lomefloxacin (LFX), sparfloxacin hydrochloride (SFX), gatifloxacin (GFX), and moxifloxacin (MFX) were developed. The present methods were first used to explore the adsorption behavior of the four investigated antibacterial agents at a hanging mercury dropping electrode (HMDE), by a direct method and secondly by a modification via their complexation with PdCl(2). For the direct method, drugs were accumulated on HMDE, and a well-defined reduction peak was obtained in Britton-Robinson buffer of pH 7 for LFX and SFX, and pH 6 for GFX and MFX. The adsorptive stripping response was evaluated as a function of some variables such as the scan rate, pH, accumulation time and potential. For the modified method, the adsorptive behavior of Pd(II)-4-quinolone complexes at the HMDE developed a strippining voltammetry peak at a more negative potential than that of the free Pd(II) ions (-1.05 V). The limits of detection (LOD) were 2 x 10(-8) M, while the limits of quantification (LOQ) were 6 x 10(-8) M for the investigated drugs. The methods were applied to the determination of LFX, SFX, GFX, and MFX in biological samples and pharmaceutical preparations, and also compared with the official reference methods. Complete validation of the proposed methods was also done.


Topical Timolol Inhibits Corneal Neovascularization in Rabbits.
Timolol is a non-selective beta-adrenergic antagonist that is similar to propranolol. The mechanism through which these drugs act on the regression of neovascularization is largely unknown. However, it is thought that the drugs may act through vascular endothelial growth factor signaling, vasoconstriction, and vascular endothelial cell apoptosis. The aim of this study was to determine the effect of timolol on corneal neovascularization in rabbits. Neovascularization was induced in the eyes of 20 rabbits. Next, the rabbits were divided into two groups: the timolol (experimental) group received eye drops containing timolol 0.5% twice per day; and the saline (control) group received saline drops twice per day for two weeks. After 7 days, the mean area of corneal neovascularization (presented as a percentage relative to baseline) was significantly lower in the timolol group than in the saline group (4.63 ± 4.61% versus 58.39 ± 6.31%, P < 0.001). After 2 weeks, the mean area of corneal neovascularization was 0.85 ± 1.33% in the timolol group and 1.73 ± 2.06% in the saline group (P = 0.315). After the first week of treatment, timolol significantly reduced the area of neovascularization compared to control. Timolol may increase the rate of recovery from corneal neovascularization.


Promoting safe use of equipment for neurogenic bowel management.
Nurses have a responsibility to monitor patient safety related to the use of equipment. Existing bowel care/shower chairs used by persons with neurogenic bowel can pose serious safety risks for patients. Twenty-four percent of persons with spinal cord dysfunction reported development of pressure ulcers and cuts from the seats, and 35% reported a history of falls from bowel care/shower chairs. Of those who reported injuries due to falls, more than 23% reported that they were hospitalized from 1 month to 4 years due to injuries from the fall. Many of the pressure ulcers and falls that occur from the use of bowel care equipment can be prevented. A combination of design flaws and user error are responsible for these safety risks. Design flaws in existing equipment include seat design, seat configuration, footrests, armrests, hand rims that are difficult to propel when wet, unreliable brakes, and chair frame instability. User error that contributes to pressure ulcers relates to poor posture in the chair. User error that contributes to patient falls relates to leaning over to wash the feet and lack of maintenance of air pressure in the tires, which affects the brakes. A series of research and development projects enabled the authors to design a new bowel care/shower chair that incorporates many new features and inventions to enhance patient safety.


Repopulation of the postmitotic nucleolus by preformed RNA.
This study is concerned with the fate of the nucleolar contents, particularly nucleolar RNA, during mitosis Mitotic cells harvested from monolayer cultures of Chinese hamster embryonal cells, KB6 (human) cells, or L929 (mouse) cells were allowed to proceed into interphase in the presence or absence (control) of 0.04-0 08 microg/ml of actinomycin D, a concentration which preferentially inhibits nucleolar (ribosomal) RNA synthesis 3 hr after mitosis, control cells had large, irregularly shaped nucleoli which stained intensely for RNA with azure B and for protein with fast green. In cells which had returned to interphase in the presence of actinomycin D, nucleoli were segregated into two components easily resolvable in the light microscope, and one of these components stained intensely for RNA with azure B. Both nucleolar components stained for protein with fast green In parallel experiments, cultures were incubated with 0.04-0 08 microg/ml actinomycin D for 3 hr before harvesting of mitotic cells, then mitotic cells were washed and allowed to return to interphase in the absence of actinomycin D. 3 hr after mitosis, nuclei of such cells were devoid of large RNA-containing structures, though small, refractile nucleolus-like bodies were observed by phase-contrast microscopy or in material stained for total protein. These experiments indicate that nucleolar RNA made several hours before mitosis persists in the mitotic cell and repopulates nucleoli when they reform after mitosis


The anti-tumor effect of folate-targeted liposome microbubbles loaded with oridonin as ultrasound-triggered tumor-targeted therapeutic carrier system.
In this study, folate receptor (FR) targeted liposome microbubbles loaded with oridonin (ORI) (F-LMB-ORI), liposome loaded with ORI (L-ORI) and liposome microbubbles loaded with ORI (LMB-ORI) were prepared. In vitro release properties, cellular uptake and cytotoxicity in HepG-2 cells as well as in vivo antitumor effects in HepG-2 cells tumor-bearing mice of F-LMB-ORI, L-ORI and LMB-ORI were evaluated upon ultrasound exposure. Results showed cytotoxicity assay on F-LMB-ORI gave IC50 of 0.508 ± 0.018 µmol/mL on HepG-2 cells and LMB-ORI; L-ORI gave IC50 of 2.424 ± 0.116 µmol/mL, 3.031 ± 0.122 µmol/mL in vitro, respectively. These drug delivery carriers were able to control the release of ORI. F-LMB-ORI exhibited higher binding to HepG-2 cells in comparison to LMB-ORI and L-ORI. F-LMB-ORI improved antitumor activity of ORI obviously in comparison to L-ORI, LMB-ORI under in vivo ultrasound. After the treatment for 14 d, the tumor inhibition ratio for F-LMB-ORI (the dose of ORI: 1.5 × 10-2 g·kg-1, once a day) was 87.6%, obviously higher than that of LMB-ORI group, L-ORI group and free ORI (the dose of ORI: 1.5 × 10-2 g·kg-1, once a day) which were 71.5%, 64.3% and 43.4%, respectively.


Nonparallel Stacks of Donor and Acceptor Chromophores Evade Geminate Charge Recombination.
We report a nonparallel stacked arrangement of donor–acceptor (D–A) pairs for prolonging the lifetime of photoinduced charge-separated states. Hydrogen–hydrogen steric repulsion in naphthalimide-naphthalene (NIN) dyad destabilizes the planar geometry between the constituent units in solution/ground state. Sterically imposed nonplanar geometry of the dyad allows the access of nonparallel arrangement of the donor and acceptor stacks having triclinic space group in the crystalline state. Antiparallel trajectory of excitons in nonparallel D–A stacks can result in lower probability of geminate charge recombination, upon photoexcitation, thereby resulting in a long-lived charge-separated state. Upon photoexcitation of the NIN dyad, electron transfer from naphthalene to the singlet excited state of naphthalimide moiety results in radical ion pair intermediates that survive >10,000-fold longer in the aggregated state (τcra > 1.2 ns) as compared to that of monomeric dyad (τcrm < 110 fs), monitored using femtosecond transient absorption spectroscopy.


Aesthetic surgery of the aging neck: options and techniques.
As the surgeon learns to address the aging changes of the forehead, brows, eyelids and cheeks, the natural progression is to understand aging of the lower one-third of the face and aging of the neck. An understanding of surface anatomy, a review of the underlying anatomical changes of aging and an overview of the palette of procedures applicable to the aging of the neck are presented to introduce the surgeon to this important part of the aging face.


Nursing students and sport: health promotion, team building and professional skills education.
Nursing profession requires a complex set of capacities, such as team building, reaching a common goal, understanding of different roles, good communication, and positive conflict resolution. Teaching this kind of competencies during the university course is challenging. Team sports require quite similar abilities to those of a nursing tam. Introducing team sport into academic course could contribute to teach and to train these key competencies to nursing students. To improve important personal skills for nursing profession through team sport. Students were invited to participate in team sport activities. To promote autonomy and initiative students were asked to create two teams (soccer and volleyball), to organize groups, to assign roles, and to choose the uniform. The two teams participated to a city university sports championship. Nursing school supported students in all the activities. At the end of the sport season, an anonymous questionnaire was administered to students. 24/107 nursing students (22.4%) participated, 13/24 males (54%) and 11/24 females (46%), (mean age 22.42 years, SD 2.28). 15/24 students (62.5%) attended all the training sessions. Students satisfaction was generally very positive in terms of physical wellness (87.5%), team building (95.8%), sharing and working for common goals (100%), and positive conflict resolution (100%), both when witnessed and experienced. All students would repeat and recommend the experience. Results were generally positive, but further research is necessary to evaluate potential positive effects in terms of nursing activities. Nursing course is very challenging, and promoting team-sport activities among students could have positive impact on professional skills education.


Outcomes and cost-minimization analysis of cement spacers versus expandable cages for posterior-only reconstruction of metastatic spine corpectomies.
Reconstruction of the thoracolumbar spine after tumor corpectomy can be accomplished using either an expandable metallic cage (EC) or a polymethylmethacrylate (PMMA) cement spacer. Few studies have compared the relative successes between these two forms of reconstructions in the management of metastatic spine disease (MSD). The purpose of this study was to compare both the outcomes and costs of EC and PMMA spacers in the treatment of MSD. We hypothesized that the rate of complications and revision surgery when using PMMA spacers to reconstruct the spine after corpectomy for MSD would be equivalent to use of an EC, with lower implant and operating room (OR) costs. A single surgeon performed 65 vertebral corpectomies for MSD requiring anterior column reconstruction from 2007-2014. Charts were retrospectively reviewed and no patients were excluded. All resections were single-stage resections/reconstructions of the vertebral body through a posterior-only approach. Outcomes evaluated included perioperative complications, intraoperative time, postoperative survival, subsequent reoperations, and changes in radiographic spinal alignment. Thirty-six patients were treated with PMMA spacers; 29 were treated with EC. Baseline age, BMI, comorbidities, and disease severity as measured by Tokuhashi scores were equivalent between treatment groups. The cohorts had no significant differences in operative complications, blood loss, postoperative survival, number of subsequent reoperations, or changes in radiographic alignment. PMMA patients had a significantly shorter mean operative duration (328.6 vs. 241.1 min, P<0.001). Institutional implant cost savings were $4,355 favoring the PMMA cohort ($75 for cement vs. $5,000 for cage). Mean OR time savings were calculated to be $2,001 less for the PMMA cohort. Total cost minimization per PMMA case was thus $6,356, which was robust in 2-way sensitivity analyses varying both implant costs and time costs by 30%. In the largest series of posterior-only corpectomies for MSD reconstructed with PMMA, PMMA intervertebral spacers provided equivalent stability and longevity to EC, at a fraction of the cost. PMMA showed excellent durability while minimizing costs by $6,356 per case, an important consideration as reimbursement pressures increasingly influence surgical decision making.


Harnessing robotic automation and web-based technologies to modernize scientific outreach.
Technological breakthroughs in the past two decades have ushered in a new era of biomedical research, turning it into an information-rich and technology-driven science. This scientific revolution, though evident to the research community, remains opaque to nonacademic audiences. Such knowledge gaps are likely to persist without revised strategies for science education and public outreach. To address this challenge, we developed a unique outreach program to actively engage over 100 high-school students in the investigation of multidrug-resistant bacteria. Our program uses robotic automation and interactive web-based tools to bridge geographical distances, scale up the number of participants, and reduce overall cost. Students and teachers demonstrated high engagement and interest throughout the project and valued its unique approach. This educational model can be leveraged to advance the massive open online courses movement that is already transforming science education.


Bed partners' assessment of nasal continuous positive airway pressure therapy in obstructive sleep apnea.
This study aimed to evaluate the effects of nasal continuous positive airway pressure (nCPAP) therapy on sleep and daytime symptoms of bed partners and patients with obstructive sleep apnea (OSA). A cross-sectional questionnaire survey. The sleep laboratory of a university teaching hospital. Ninety-one consecutive OSA patients within 2 to 12 months of being prescribed nCPAP. Eighty-five replies (93% of sample population) were received. Twelve patients (14% of replies) had discontinued nCPAP therapy; two patients had not yet been supplied with an nCPAP device. Seventy-one patients continued nightly nCPAP therapy. Bed partners of these patients (n = 55) answered a separate questionnaire assessing improvements in their own sleep quality, daytime alertness, mood and quality of life (questions 1 to 4), and evaluated the same parameters for the patients (questions 5 to 8). Possible scores ranged from -1 (worse) to +3 (marked improvement). Questions 1 to 4 yielded median scores of 2, 1, 1, and 2, respectively, and scores of 3, 3, 2, and 3 for questions 5 to 8. A ninth question addressing perceived changes in the quality of their relationship resulted in a median score of 2. Mean (SD) Epworth sleepiness scores improved from 14.3 (5.8) to 5.2 (4.3) in patients receiving therapy (p < 0.005). These data indicate that bed partners of OSA patients treated with nCPAP experience important improvements in symptoms and personal relationships. The findings are of practical clinical use when counseling patients with OSA and their partners on the likely impact of nCPAP therapy on their quality of life.


A pyridone derivative activates SERCA2a by attenuating the inhibitory effect of phospholamban.
The cardiac sarco/endoplasmic reticulum Ca2+-dependent ATPase 2a (SERCA2a) plays a central role in Ca2+ handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca2+-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN. The surface plasmon resonance assay revealed a direct interaction between compound A and PLN, suggesting that the binding of compound A to PLN attenuates its inhibition of SERCA2a, resulting in SERCA2a activation. This was substantiated by inhibition of the compound A-mediated increase in Ca2+ levels within the SR of HL-1 cells by thapsigargin, a SERCA inhibitor. Compound A also increased the Ca2+ transients and contraction and relaxation of isolated adult rat cardiomyocytes. In isolated perfused rat hearts, the compound A enhanced systolic and diastolic functions. Further, an infusion of compound A (30mg/kg, i.v. bolus followed by 2mg/kg/min, i.v. infusion) significantly enhanced the diastolic function in anesthetized normal rats. These results indicate that compound A is a novel SERCA2a activator, which attenuates PLN inhibition and enhances the systolic and diastolic functions of the heart in vitro and in vivo. Therefore, compound A might be a novel therapeutic lead for heart failure.


Overexpression of upstream stimulatory factor 2 accelerates diabetic kidney injury.
Diabetic nephropathy is the most common cause of end-stage renal failure in the United States. Hyperglycemia is an important factor in the pathogenesis of diabetic nephropathy. Hyperglycemia upregulates the expression of transforming growth factor-beta (TGF-beta), which stimulates extracellular matrix deposition in the kidney, contributing to the development of diabetic nephropathy. Our previous studies demonstrated that the transcription factor, upstream stimulatory factor 2 (USF2), was upregulated by high glucose, which bound to an 18-bp sequence in the thrombospondin 1 (TSP1) gene promoter and regulated high glucose-induced TSP1 expression and TGF-beta activity in mesangial cells, suggesting that USF2 might play a role in the development of diabetic nephropathy. In the present studies, we examined the effect of overexpression of USF2 on the development of diabetic nephropathy. Type 1 diabetes was induced in USF2 transgenic mice [USF2 (Tg)] and their wild-type littermates (WT) by injection of streptozotocin. Four groups of mice were studied: control WT, control USF2 (Tg), diabetic WT, and diabetic USF2 (Tg). Mice were killed after 15 wk of diabetes onset. At the end of studies, control USF2 (Tg) mice ( approximately 6 mo old) exhibited increased urinary albumin excretion. These mice also exhibited glomerular hypertrophy, accompanied by increased TSP1, active TGF-beta, fibronectin accumulation in the glomeruli compared with control WT littermates. Type 1 diabetes onset further augmented the urinary albumin excretion and glomerular hypertrophy in the USF2 (Tg) mice. These findings suggest that overexpression of USF2 accelerates the development of diabetic nephropathy.


MiR-185 inhibits 3T3-L1 cell differentiation by targeting SREBP-1.
Adipogenesis involves a highly orchestrated series of complex events in which microRNAs (miRNAs) may play an essential role. In this study, we found that the miR-185 expression increased gradually during 3T3-L1 cells differentiation. To explore the role of miR-185 in adipogenesis, miRNA agomirs and antagomirs were used to perform miR-185 overexpression and knockdown, respectively. Overexpression of miR-185 dramatically reduced the mRNA expression of the adipogenic markers, PPARγ, FABP4, FAS, and LPL, and the protein level of PPARγ and FAS. MiR-185 overexpression also led to a notable reduction in lipid accumulation. In contrast, miR-185 inhibition promoted differentiation of 3T3-L1 cells. By target gene prediction and luciferase reporter assay, we demonstrated that sterol regulatory element binding protein 1 (SREBP-1) may be the target of miR-185. These results indicate that miR-185 negatively regulates the differentiation of 3T3-L1 cells by targeting SREBP-1, further highlighting the importance of miRNAs in adipogenesis.


Preparation, characterization of C/Fe-Bi2WO6 nanosheet composite and degradation application of norfloxacin in water.
A novel C/Fe-Bi2WO6 nanosheet composite photocatalyst combining the properties of both semiconductor and Fenton like catalyst was prepared via a two-step method involving Resin carbonization and hydrothermal process. The samples were characterized by X-ray diffraction (XRD), scanning electronic microscopy (SEM) and energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), UV-vis diffuse reflectance spectra (DRS), X-ray photoelectron spectroscopy (XPS), Fourier transformed infrared spectroscopy (FT-IR) and nitrogen adsorption-desorption measurements. Structure analyses indicated that C/Fe-Bi2WO6 presented a nanosheet and macro-meso dual porosity structure. The as-prepared composite exhibited high efficiency in the photocatalytic decomposition of norfloxacin (NOR) by the assistance of H2O2. This method is promising due to its inexpensive starting materials and good photocatalyst for degradation of emerging micropollutants.


Influencing relatives to respect donor autonomy: Should we nudge families to consent to organ donation?
Refusing consent to organ donation remains unacceptably high, and improving consent rates from family or next-of-kin is an important step to procuring more organs for solid organ transplantation in countries where this approval is sought. We have thus far failed to translate fully our limited understanding of why families refuse permission into successful strategies targeting consent in the setting of deceased organ donation, primarily because our interventions fail to target underlying cognitive obstacles. Novel interventions to overcome these hurdles, incorporating an understanding of cognitive psychology and behavioral change therapy, may be beneficial. One potential intervention is to use the concept of nudge theory, where decision-making is influenced by encouraging positive reinforcement and indirect suggestion. Purposefully nudging families to given consent for organ donation by understanding, and then overcoming, their inherent cognitive biases is novel but also controversial. This article explores the roles of relatives in decisions about organ donation, how nudge theory translates to organ donation and discusses the arguments for and against its application.


Distance geometry analysis of the N.M.R. evidence on the solution conformation of bleomycin.
Conformational constraints derived from n.m.r. experiments, X-ray data and the known stereochemistry have been used to investigate by the distance geometry method the range of allowed solution conformations for Cu(II):P-3A (a biosynthetic precursor of bleomycin), Fe(II):bleomycin:carbon monoxide, and Zn(II):bleomycin. The experimental data have been found to be self-consistent and lead to the following observations. 1) Designation of the ligands and the dihedral angles available from vicinal coupling constants are not sufficient to define uniquely the geometry around the metal. 2) When only five bleomycin ligands are invoked (e.g. Cu(II):P-3A or Fe(II):bleomycin:carbon monoxide) there is considerable freedom in the allowed coordination scheme around the metal, but some regions of the molecule have well determined conformation. 3) Introduction of a sixth bleomycin ligand, as in Zn(II):bleomycin, considerably constrains the conformational freedom of the groups coordinated to the zinc. The utility of the distance geometry approach for analysis of data and design of experiments is discussed.


Narrative review: do state laws make it easier to say "I'm sorry?".
Initiatives intended to reduce the frequency and impact of medical errors generally rely on recognition and disclosure of medical errors. However, fear of malpractice liability is a barrier to physician disclosure. Some U.S. state legislatures have attempted to encourage physicians to disclose medical errors by enacting "apology laws." The authors reviewed the codified statutes of each of the 50 states and the District of Columbia to determine the prevalence and characteristics of such apology laws. They found that many states have recently adopted apology laws and that there is variability in these laws. The authors review some of the important differences in these laws and explore the potential impact of apology laws.


Combination curcumin and vitamin E treatment attenuates diet-induced steatosis in Hfe-/- mice.
To investigate the synergistic hepato-protective properties of curcumin and vitamin E in an Hfe-/- high calorie diet model of steatohepatitis. Hfe-/- C57BL/6J mice were fed either a high calorie diet or a high calorie diet with 1 mg/g curcumin; 1.5 mg/g vitamin E; or combination of 1 mg/g curcumin + 1.5 mg/g vitamin E for 20 wk. Serum and liver tissue were collected at the completion of the experiment. Liver histology was graded by a pathologist for steatosis, inflammation and fibrosis. RNA and protein was extracted from liver tissue to examine gene and protein expression associated with fatty acid oxidation, mitochondrial biogenesis and oxidative stress pathways. Hfe-/- mice fed the high calorie diet developed steatohepatitis and pericentral fibrosis. Combination treatment with curcumin and vitamin E resulted in a greater reduction of percent steatosis than either vitamin E or curcumin therapy alone. Serum alanine aminotransferase and non-alcoholic fatty liver disease (NAFLD) activity score were decreased following combination therapy with curcumin and vitamin E compared with high calorie diet alone. No changes were observed in inflammatory or fibrosis markers following treatment. Epididymal fat pad weights were significantly reduced following combination therapy, however total body weight and liver weight were unchanged. Combination therapy increased the mRNA expression of AdipoR2, Ppar-α, Cpt1a, Nrf-1 and Tfb2m suggesting enhanced fatty acid oxidation and mitochondrial biogenesis. In addition, combination treatment resulted in increased catalase activity in Hfe-/- mice. Combination curcumin and vitamin E treatment decreases liver injury in this steatohepatitis model, indicating that combination therapy may be of value in NAFLD.


Prolactin-secreting pituitary adenomas: CT appearance in diffuse invasion.
The authors describe 2 diffusely invasive prolactin-secreting pituitary adenomas which produced marked destruction of the base of the skull thought to be diagnostic of chordoma on computed tomography (CT). Failure to recognize this pattern led to biopsy, which was diagnostic. The authors emphasize the need to recognize this rare growth pattern of diffusely invasive pituitary adenoma on CT.


Management of multifocal primary cutaneous CD30 anaplastic large cell lymphoma.
Primary cutaneous CD30(+) anaplastic large cell lymphoma in adults is rare, but the prognosis is generally excellent. Skin lesions may be localized or, less commonly, multifocal. Although not extensively reported, multifocal primary cutaneous anaplastic large cell lymphoma tends to relapse after systemic chemotherapy and is generally considered more prone to progress to extracutaneous involvement than the localized disease. We report the case of a 21-year-old woman with primary cutaneous CD30(+) anaplastic large cell lymphoma manifesting as widespread papules and nodules. Despite remaining localized to the skin, the disease relapsed after multiple chemotherapy regimens and autologous stem-cell transplantation. Treatment with an experimental anti-CD30 monoclonal antibody was successful. Review of this case and similar cases illustrates that traditional combination chemotherapy may not be best. Newer treatments, including anti-CD30 monoclonal antibodies, show promise. However, further study is needed to develop optimal therapeutic strategies.


The phagocytic process and the role of complement in host defense.
Three lines of defense play an integral role in host defense. The mechanical barrier (skin and mucous membrane: first line), non-specific defense (phagocytic cells non-specific humoral factors) and the specific line of defense. Phagocytic cells act in phases: chemotaxis, attachment of the bacteria to the membrane of the phagocytic cells, ingestion, killing and digestion. Attachment of the particle to receptors is only optimal when the bacteria are loaded with antibodies (IgG) and/or activated complement factors (C3b, C3Bbi), because the phagocyte has receptors for these opsonins (Fc, and C receptors). The late complement factors are also able to kill and lyse certain bacteria without phagocytes. The killing mechanism of the phagocyte is complex. It is oxygen dependent and oxygen independent. Presumably toxic oxygen species are most important to kill bacteria by phagocytes.


Carbapenem-resistant enterobacteriaceae: an emerging problem in children.
Antibiotic resistance among gram-negative bacteria has reached critical levels. The rise of carbapenem resistance in Enterobacteriaceae carrying additional resistance genes to multiple antibiotic classes has created a generation of organisms nearly resistant to all available therapy. Carbapenem-resistant Enterobacteriaceae (CRE) infections are known to be associated with significant morbidity and mortality, and these pathogens have now made their way to the most vulnerable populations, including children. This review provides a brief overview of CRE, with a focus on CRE infections in children, and highlights available data on the epidemiology, clinical characteristics, carbapenemase types, risk factors, treatment, and outcomes of these multi-drug resistant infections in the pediatric population.


Slow cellular dynamics in MDCK and R5 cells monitored by time-lapse atomic force microscopy.
We have examined dynamic events that occur on a time scale of minutes in an epithelial monolayer of Madine-Darby Canine Kidney (MDCK) cells and in ras-transformed MDCK cells by atomic force microscopy (AFM). Cells were imaged under physiological conditions, and time-lapse movies representing approximately 60 s real time per frame were assembled. In normal MDCK cells, two types of protrusions in the apical plasma membrane exhibit dynamic behavior. First, smooth bulges formed transiently over the time scale of minutes to tens of minutes. Second, spike-like protrusions appear initially as bulges, extend well above the apical surface and, finally, seem to detach. R5, an oncogenic transformant derived from MDCK cells, grows very flat on glass. During AFM imaging, these cells sometimes round up and detach from the substrate. In light microscopic observations of parallel preparations, cells rarely detach, suggesting that this is an active response of these cells to irritation by the AFM tip. R5 cells often extend processes that are supported by actin stress fibers. During imaging with the AFM, these processes withdraw at a rate of 1-5 microns/min, similar to that observed by light microscopy. During the withdrawal, movement of the stress fibers can be clearly seen. In the flat periphery of these cells, the transport of intracellular particles along cytoskeletal elements was seen. In addition, we have observed two types of wave-like movements through the cell, which appear to be an organized rearrangement of cytoplasm. One type of wave moves radially out from center of the cell while the other moves circularly along the cell periphery.


DNA polymorphisms in the epsilon- and gamma-globin gene regions in Asian macaques.
DNA polymorphisms in the epsilon- and gamma-globin gene regions in nine Asian macaques (Macaca fuscata, M. mulatta, M. nemestrina, M. cyclopis, M. fascicularis, M. arctoides, M. radiata, M. maura, and M. assamensis) were examined using several different restriction endonucleases and the human epsilon and gamma IVS2 probes. M. fuscata and M. mulatta had highly polymorphic sites (BglII and HincII, respectively) in the epsilon-globin gene region. The BamHI site in the gamma-globin gene region was highly polymorphic in M. mulatta, while the BglII and HindIII sites in the gamma-globin gene region were highly polymorphic in M. fuscata and M. mulatta. The presence of the gamma-globin gene triplication was frequently observed in M. fuscata. The gain or loss of an additional BglII site between two gamma-globin genes in Asian macaques seems to be very meaningful for discussing genetic relationships among them.


[Protocol for health surveillance of workers exposed to repetitive arm movements].
Repetitive movements of the upper limbs at work can cause the onset of musculo-skeletal disorders and therefore an adequate planning of health surveillance is needed. A Work Group on this problem was constituted in Brescia, Italy, following the great interest raised by recent scientific meetings on this topic. The aim of the Group was to prepare a proposal for a health surveillance protocol for the use of Occupational Health Physicians. Health surveillance for the prevention of upper limb disorders must be based on the degree of risk. The risk assessment procedure should be based on the methodology currently available for ergonomic analysis and should also consider the frequency of upper limb disorders in the exposed workers. In case of moderate risk, it is necessary to identify hyper-susceptible individuals, in order to reduce exposure to repetitive movements by means of an adequate task fitness evaluation and suitable health education programmes. In situations of medium-to-high risk, a specific programme of health surveillance must be planned in order to identify early disorders and prevent the onset of more severe damage using task fitness evaluation and rehabilitation therapies. The appropriate diagnostic procedure is indicated for this purpose and a classification is proposed to divide the upper limb disorders into two stages, according to the clinical picture: a first acute-subacute stage, which is potentially reversible, and a chronic-subchronic stage, which is non-reversible. Legal reports are required according to the stage of the disease identified and must be supported by an adequate risk assessment.


Electron microscopy of some special cell contracts in yeasts.
Anastomosis in Endomycopsis javanensis and some other filamentous yeasts was brought about by contact of a denticle from one cell with the wall of another cell, resulting in the disappearance of the outer layer and the thickening of the inner layer of the cell wall of the contacted cell. Another form of contact between cells was the penetration of one cell by a denticle on another cell which had grown out to a stalk; this occurred between cells of E. javanensis and between cells of this species and other yeast species.


Covariation of alpha 2-adrenoceptor density and function following irreversible antagonism with EEDQ.
1. Administration of the irreversible antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, (EEDQ, 2 mg kg-1, i.p.) to mice reduced binding of [3H]-RX 821002 (2-methoxy-idazoxan) to alpha 2-adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days. 2. EEDQ administration also resulted in the loss of the sedative effect of the alpha 2-adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonist-induced sedation returned to control values by 8 days post EEDQ administration. 3. EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg-1, i.p.). Medetomidine-induced hypothermia returned to control values by 12 days post EEDQ administration. 4. Pretreatment with the selective alpha 2-adrenoceptor antagonist, RX 821002 (0.1-3.0 mg kg-1, i.p.) 45 min before EEDQ prevented the loss of alpha 2-adrenoceptors as well as the blockade of medetomide-induced sedation and hypothermia by EEDQ. 5. The results of these experiments indicate that there is significant receptor reserve for alpha 2-adrenoceptor-mediated behavioural and physiological responses.


"Silent" hepatitis B virus mutants are responsible for non-A, non-B, non-C, non-D, non-E hepatitis.
Since the recent introduction of diagnostic kits for hepatitis C and E, some cases of non-A, non-B, non-C, non-D, non-E hepatitis (so-called hepatitis F) have been revealed. We attempted to demonstrate that so-called hepatitis F is caused by hepatitis B virus (HBV) variants. Polymerase chain reaction (PCR) was used to amplify serum HBV DNAs from 20 patients with acute hepatitis and 20 patients with chronic hepatitis who had been diagnosed as having so-called hepatitis F on the basis of conventional serological markers. The PCR technique successfully amplified HBV DNAs in 18 (90%) cases of acute hepatitis and 17 (85%) cases of chronic hepatitis. Sequencing of HBV DNAs of six patients (acute 3, chronic 3) revealed equally a T-to-C mutation of DR2 and an 8-nucleotide deletion of the 3'-terminus of the X gene coding region, giving rise to the generation of a C-terminally truncated X protein and probable damage to the enhancer II/core promoter elements. These mutations of the X gene coding region may lead to suppression of replication and expression of HBV DNAs. Thus virtually all cases of so-called hepatitis F appear to be caused by "silent" HBV mutants, at least in Japan.


An evolutionary model of the environmental conditions that shape the development of prosociality.
The current review presents a model for how prosocial development is driven by sociocognitive mechanisms that have been shaped by natural selection to translate critical environmental factors into locally adaptive levels of prosociality. This is done through a synthesis of two existing literatures. Evolutionary developmental psychologists have demonstrated a biological basis for the emergence of prosocial behavior early in youth, and work based on social learning theory has explored how social experiences can influence prosociality across development. The model forwarded organizes this latter literature in a way that is specific to how the biological mechanisms underpinning prosociality have evolved. This consists of two main psychological mechanisms. 1) A domain-specific program that is responsive to environmental factors that determine the relative success of different levels of prosociality. It uses the local prevalence of prosocial others (i.e., support) and expectations for prosocial behavior (i.e., structure) to guide prosocial development. 2) The domain-general process of cultural learning, by which youth adopt local social norms based on the examples of others. Implications and hypotheses are articulated for both the sociocognitive structure of the individual and the role of social contexts.


How expert physicians would wish to be treated if they had genitourinary cancer.
A questionnaire describing six clinical scenarios was mailed to urologists (in Britain, Canada, and the United States) and to radiation and medical oncologists in the United States, who practice genito-urinary (GU) oncology. In each scenario, the surgeon or physician was asked to consider himself as a patient with bladder, prostate, or kidney cancer, and to select his own treatment. Accompanying each scenario were one or two clinical trials for which the physician would be eligible. He was asked to state if he would agree to be randomized in each trial, and if he refused, to state his reasons. We found that (1) there were major differences of opinion about management for each scenario; (2) choice of treatment was influenced more by specialty training or geographic location than by the results of previous clinical trials (which are available to all); (3) British urologists tended to be less aggressive than their North American colleagues, with respect to the use of radical surgery and chemotherapy; (4) acceptance of clinical trials ranged from 3% to 60%; and (5) agreement to clinical trials was quite poor even when they were designed to compare the most popular options for management. This physician surrogate method is a valuable tool in assessment of the degree of consensus amongst expert physicians and in the determination of whether new clinical trials address important areas of controversy.


Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia.
Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy with poor prognosis. We previously showed synergistic antileukaemic interaction between exportin 1 (XPO1) inhibitor KPT-330 (Selinexor) and Bcl-2 inhibitor venetoclax (ABT-199) in preclinical models of AML, which was partially meditated by Mcl-1, although the full mechanism of action remains unknown. In this study, using real-time RT-PCR and Western blot analysis, we show that inhibition of XPO1 via KPT-330 or KPT-8602 (Eltanexor) decreases the mRNA and protein levels of c-Myc, CHK1, WEE1, RAD51 and RRM2. KPT-330 and KPT-8602 induce DNA damage, as determined by alkaline comet assay. In addition, we demonstrate that venetoclax enhances KPT-330- and KPT-8602-induced DNA damage, likely through inhibition of DNA damage repair. This study provides new insight into the molecular mechanism underlying the synergistic antileukaemic activity between venetoclax and XPO1 inhibitors against AML. Our data support the clinical evaluation of this promising combination therapy for the treatment of AML.


Screening for human T cell leukaemia/lymphoma virus among blood donors in Sweden: cost effectiveness analysis.
To analyse the cost effectiveness of a national programme to screen blood donors for infection with the human T cell leukaemia/lymphoma virus. Three models for calculating the costs and benefits of screening were developed. The first model analysed the cost of continuously testing all donations; the second analysed the cost of initially testing new blood donors and then retesting them after five years; the third analysed the cost of testing donors only at the time of their first donation. Patients who had received blood components from donors confirmed to be infected with the virus were offered testing. Sweden. Prevalence of infection with the virus among blood donors, the risk of transmission of the virus, screening costs, and the outcome of infection. 648 497 donations were tested for the virus; 1625 samples tested positive by enzyme linked immunosorbent assay. 6 were confirmed positive by western blotting. The prevalence of infection with the virus was 2/100 000 donors. 35 patients who had received blood infected with the virus were tested; 3 were positive. The cost of testing every donation was calculated to be $3.02m (1.88m pounds); this is 18 times higher than the cost of testing new donors only, and only 1 additional positive donor would be discovered in 7 years. Regardless of the model used, screening was estimated to prevent only 1 death every 200 years at a minimum cost of $36m (22.5m pounds). Based on these estimates the Swedish National Board of Health and Welfare decided that only new blood donors would be screened for infection with the virus.


Experience with perioperative pirfenidone for lung cancer surgery in patients with idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse lung disease associated with an increased risk of lung cancer. Patients with IPF sometimes develop a life-threatening acute exacerbation of IPF (AE-IPF) after lung cancer surgery. In this retrospective study, pirfenidone, an antifibrotic agent, was perioperatively administered to IPF patients with lung cancer with the aim of preventing postoperative AE-IPF, and the feasibility and clinical outcomes were investigated. Twelve IPF patients with concomitant lung cancer who received perioperative pirfenidone treatment (PPT) for lung cancer surgery were retrospectively investigated. Sixteen IPF patients undergoing lung cancer surgery without PPT were analyzed as historical controls. Compared to the controls, the PPT patients had a more severely impaired preoperative pulmonary function and a larger number of limited pulmonary resections. There was a significant preoperative decrease in the serum KL-6 levels of the PPT patients. No severe pirfenidone-related complications or IPF-related events occurred in the PPT patients, while six control patients developed AE-IPF (P = 0.0167). A quantitative histopathological evaluation of resected lung specimens found that tissue changes associated with IPF were significantly fewer in the PPT patients (P = 0.021). PPT is a feasible perioperative treatment for IPF patients with lung cancer. Its effectiveness in preventing postoperative AE-IPF thus warrants prospective verification.


Retroperitoneal abscess complicated by acupuncture: case report.
With acupuncture treatment becoming an increasingly popular analgesic, there have been increasing reports on its associated complications. Although pneumothorax is the most frequently reported injury caused by acupuncture needles, infectious complications may not be uncommon. Most infectious complications show less serious clinical manifestations than pneumothorax, but retroperitoneal or intraabdominal abscess caused by acupuncture may be much more serious conditions. We experienced a 56-yr-old male diabetic patient presenting with serious retroperitoneal abscess after acupuncture treatments. Emergency operative drainage with adequate antibiotic therapy was performed. Bacterial culture of blood and closed pus specimens recovered Klebsiella pneumoniae. In addition to application of better knowledge on anatomy, appropriate antiseptic practice by practitioners will reduce many serious complications associated with acupuncture.


Excretion rates of antibiotics in milk of sheep and their effect on yogurt production.
Excretion rates in milk of sodium penicillin G, streptopenicillin, oxytetracycline, and chlortetracycline given to sheep by intramuscular injection or intramammary infusion were studied. When given by intramuscular injection, penicillin G and streptopenicillin were excreted in milk for 24 h, oxytetracycline for 38 h, and chlortetracycline for 72 h. The corresponding times following intramammary infusion were 72 to 86 h, 72 to 86 h, 96 to 100 h, and 110 to 120 h. Concentrations in milk of penicillin, streptopenicillin, and oxytetracycline given by intramuscular injection made it unsuitable for yogurt production for 24 h. Chlortetracycline, although excreted in milk longer, did not affect yogurt production. When antibiotics were given by intramammary infusion, they were excreted in milk in concentrations harmful for yogurt production for 72, 72, 96, and 116 h.


The SF-36 general health status survey documents the burden of osteoarthritis and the benefits of total joint arthroplasty: but why should we use it?
To document the disease burden of osteoarthritis and the benefits of total joint replacement by using the Short Form Health Survey (SF-36) general health status survey and evaluate other factors that could affect scores. Prospective study. All patients scheduled for primary total hip arthroplasty (THA) or total knee arthroplasty (TKA) (n = 622 preoperatively) in 2 years were surveyed using the SF-36, which assesses health-related quality of life (HRQOL) in patients' physical and social functioning and mental health. Follow-up surveys were administered 12 months after surgery to all patients and 3 and 24 months after surgery to a subset of patients. Preoperatively, patient scores were significantly lower than normative scores in the physical functioning, bodily pain, and social functioning domains. Preoperative scores were not different between THA and TKA patients. Women scored lower than men. Comorbid conditions were weakly associated with low SF-36 scores. Postoperatively, the largest incremental improvement in scores was seen at 3-month follow-up. Scores improved sooner and more substantially in THA vs TKA patients and in men vs women, paralleling improvement in clinical and subjective ratings of postoperative physical function and pain. The SF-36 has the sensitivity to document improvement in HRQOL after surgery and to reveal differences in THA vs TKA and in men vs women. However, routine use of outcome assessment instruments to monitor this patient population is costly and unjustified in our current healthcare environment.


Streamlined Efficient Synthesis and Antioxidant Activity of γ-[Glutamyl](n≥1)-tryptophan Peptides by Glutaminase from Bacillus amyloliquefaciens.
As a group of naturally occurring peptides in various foods, γ-glutamyl peptides possess a unique Kokumi taste and health benefits. However, few studies have focused on the functionality of γ-glutamyl peptides. In this study, the γ-[glutamyl] (n=1, 2, 3)-tryptophan peptides were synthesized from a solution of glutamine (Gln) and tryptophan (Trp) employing L-glutaminase from Bacillus amyloliquefaciens. Four different γ-glutamyl peptides were identified from the reaction mixture by UPLC-Q-TOF-MS/MS. Under optimal conditions of pH 10, 37 °C, 3 h, 0.1 mol/L Gln: 0.1 mol/L Trp = 1:3, and glutaminase at 0.1% (m/v), the yields of γ-l-glutamyl-l-tryptophan (γ-EW), γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEW) and γ-l-glutamyl-γ-l-glutamyl-γ-l-glutamyl-l-tryptophan (γ-EEEW) were 51.02%, 26.12% and 1.91% respectively. The antioxidant properties of the reaction mixture and the two peptides (γ-EW, γ-EEW) identified from the reaction media were further compared. Results showed that γ-EW exhibited the highest DPPH•, ABTS•+ and O2•--scavenging activity (EC50 = 0.2999 mg/mL, 67.6597 μg/mL and 5.99 mg/mL, respectively) and reducing power (EC50 = 4.61 mg/mL), while γ-EEW demonstrated the highest iron-chelating activity (76.22%). Thus, the synthesized mixture may be used as a potential source of antioxidant peptides for food and nutraceutical applications.


Purification of Tetrahymena nuclei by sedimentation at unit gravity.
This protocol provides a method for purification of Tetrahymena nuclei using sedimentation at unit gravity. It is useful for applications where purity of micro- and macronuclei is required beyond that which is typically achieved by differential sedimentation alone. When differential sedimentation is followed by sedimentation at unit gravity, micro- and macronuclei can be purified to virtual homogeneity. This method also permits the purification of homogeneous populations of developing new macronuclei (anlagen) and distinct classes of micronuclei from various stages of conjugation.


Palytoxin both induces and inhibits the release of histamine from rat mast cells.
Palytoxin (PTX) is a potent releaser of histamine from rat mast cells. The concentration response curve is bell-shaped with its range between 0.05 ng/ml and 5 micrograms/ml and its maximum at 50 ng/ml. The release of histamine by PTX is specific because (a) heat-inactivated (50 degrees C) mast cells are insensitive to PTX, and (b) extracellular calcium is essential. Removal of extracellular potassium as well as the presence of borate shifts the curve to the left by factor of 10. At higher concentrations (5 micrograms/ml), PTX inhibits the release of histamine due to compound 48/80, MCD-peptide, Con-A, ionophore A-23187, and PTX itself.


Phase II study of cisplatin and continuous-infusion 5-fluorouracil and bleomycin for recurrent and metastatic head and neck squamous-cell carcinoma.
5-Fluorouracil (5-FU) and bleomycin (BLM) are active agents in head and neck squamous-cell cancer (H-N-scc). Less toxicity and an enhanced activity have been reported when these agents are administered by continuous infusion (CI), with or without a bolus of cisplatin (CDDP), another active agent. Thirty-three patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated with a combination regimen including CDDP (100 mg/m2) on day 1 plus BLM (15-mg bolus followed by 16 mg/m2/day by CI) and 5-FU (650 mg/m2/day by CI) on days 1-5 every 3 weeks. Thirty-one patients were evaluable for toxicity and response. The response rate (RR) was 15% (5 of 31), with one complete response (CR) and four partial responses (PRs), at a confidence interval of 95% (0-34%). Four of the five responders had not received previous radiotherapeutic treatment. Toxicity was deemed acceptable; nausea and vomiting and stomatitis were moderate. Only one patient had irreversible renal toxicity, after two cycles of chemotherapy. No symptomatic lung toxicity was observed. Good antitumour activity was noted for previously untreated disease (3 of 4; 75% RR). This combination of drugs proved to be inactive, however, in previously irradiated recurrent and/or metastatic H-N-scc (1 of 25; 4% RR). These results underscore the need to be extremely attentive to different patient populations when selecting therapeutic schedules and when analyzing reported results.


Perceived efficacy, conscious fear of death and intentions to tan: not all fear appeals are created equal.
According to the terror management health model, conscious thoughts of death motivate productive health behaviours when the targeted behaviour is perceived as an effective route for mitigating the threat and removing death-related thought from focal awareness. The present study thus examined whether messages manipulating the efficacy of a health behaviour moderate health outcomes when participants are presented with a fear appeal that makes death thought conscious. A 3 (fear appeal: cancer vs. appearance vs. neutral) × 2 (delay vs. no delay) × 2 (effective vs. non-effective) between-subjects ANOVA was conducted. Beach patrons were randomly assigned to a cancer, appearance, or neutral-threat fear appeal followed by a delay or no delay. Subsequently, they read messages highlighting the effectiveness or ineffectiveness of sun protection behaviours and reported their intentions to engage in those behaviours. When fear appeals primed conscious thoughts of death, framing sun protection as ineffective decreased sun protection intentions relative to framing sun protection as effective. In contrast, fear appeals that did not consciously prime death, or appeals followed by a delay that allowed thoughts of death to fade from consciousness, did not interact with efficacy messages. The findings revealed that messages impacting sun protection efficacy moderated sun protection intentions only when death was conscious. The findings have implications for understanding the conditions that render certain fear appeals, and accompanying messages of efficacy, more influential than others.


Telangiectasia in aluminium workers: a follow up.
A five step investigation was carried out to gain a better understanding of the morbidity that accompanied the development of telangiectasia on aluminium workers and to find its cause. Fifty workers with multiple telangiectasia when matched with normal controls showed the same amount of illness except that evidence of ischaemia on the ECG was found in nine cases and one control. The cases did not show an excess of abnormal biochemical tests. The basic histopathological lesion affected the surrounding tissue rather than the vessels themselves. Working in the current environment and wearing masks seems to protect young workers from developing the lesions. The Soderberg and not the prebake process was associated with the lesions; the causative agent is probably a gas that contains both hydrocarbons and fluoride components emitted from the electrolytic reactors.


[Update on the treatment of articular cartilage lesions in the knee].
Despite articular cartilage lesions being common, there is no evidence-based treatment protocol for them. The preoperative assessment must diagnose all of the concurrent pathologies that need to be treated at the same time. Several types of treatments exist, and each has its advantages and disadvantages. First-line therapy consists of well-conducted conservative treatment. Surgical treatment is the second choice. It is chosen according to the size of the lesion, its depth, damage to the subchondral bone, and the condition of the neighboring cartilage. The few studies that have compared the different methods used to treat these lesions have reported contradictory results.


Propofol affinity to mitochondrial membranes does not alter mitochondrial function.
The molecular mechanisms of hepatotoxicity after propofol anaesthesia have not been fully elucidated, although there is a relation with mitochondrial dysfunction. The action of propofol on mitochondrial hepatic functions in a rat model was evaluated by infusion for 4h with 25 and 62.5mg/kg/h propofol or 3.125ml/kg/h (vehicle). Liver mitochondrial respiratory rates were evaluated as well as mitochondrial transmembrane potential (ΔΨ), calcium fluxes, mitochondrial enzymatic activities (Complex I-V) and oxidative stress biomarkers (superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase, lipid peroxidation and the oxidised/reduced glutathione ratio). Biophysical interactions with membrane models were also performed. The mitochondrial transmembrane potential was decreased and the opening time of the mitochondrial permeability transition pore was slightly reduced for the highest dose. The activity of complex II was stimulated by propofol, which also causes fluctuations on some respiratory parameters, whereas the antioxidant system was affected in a nonspecific manner. Fluorescence quenching studies suggested that propofol is preferably located in deeper regions of the bilayer and has a high affinity to mitochondrial membranes. It is suggested that propofol interacts with liver mitochondrial membranes with mild modification in mitochondrial function.


[Clinical efficacy of using amino acids in combination with anabolic steroids for the purpose of limiting the size of a myocardial infarct].
The authors report on the experience with amino acid drugs ( alvesin -new, aminon ) used in combination with anabolic steroids (retabolil) in patients with acute myocardial infarctions. Specific protein reparative therapy was associated with a favourable course of the disease, earlier (as against the control group) normalization of the electrotopocartographic (precordial mapping) and enzymic (CPK, LDH and LDH1) parameters. The patients' faster readaptation toward exercise and a significant elevation in the hemodynamic parameters justify the advisability of including protein reparative agents into the multiple modality treatment of myocardial infarction.


Self-Supervised Generalized Zero Shot Learning for Medical Image Classification Using Novel Interpretable Saliency Maps.
In many real world medical image classification settings, access to samples of all disease classes is not feasible, affecting the robustness of a system expected to have high performance in analyzing novel test data. This is a case of generalized zero shot learning (GZSL) aiming to recognize seen and unseen classes. We propose a GZSL method that uses self supervised learning (SSL) for: 1) selecting representative vectors of disease classes; and 2) synthesizing features of unseen classes. We also propose a novel approach to generate GradCAM saliency maps that highlight diseased regions with greater accuracy. We exploit information from the novel saliency maps to improve the clustering process by: 1) Enforcing the saliency maps of different classes to be different; and 2) Ensuring that clusters in the space of image and saliency features should yield class centroids having similar semantic information. This ensures the anchor vectors are representative of each class. Different from previous approaches, our proposed approach does not require class attribute vectors which are essential part of GZSL methods for natural images but are not available for medical images. Using a simple architecture the proposed method outperforms state of the art SSL based GZSL performance for natural images as well as multiple types of medical images. We also conduct many ablation studies to investigate the influence of different loss terms in our method.


Occupational management of healthcare workers exposed to COVID-19.
The year 2020 was marked by the new coronavirus pandemic, resulting in millions of cases and deaths, placing healthcare workers at high risk of infection. The aim of this study was to describe the role of an occupational health service during coronavirus disease 2019 pandemic in an oncologic hospital and characterize the most likely sources of viral infection. The information of all healthcare workers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from 11 March to 15 December 2020 was collected through an epidemiological survey conducted during contact tracing. The data extracted included gender, age, comorbidities, occupational group, source of infection, clinical presentation, duration of the disease, need for hospitalization and persistent or late symptoms after disease or upon returning to work. Out of a total of 2300 workers, 157 were infected, consisting of nurses (36%), nurse assistants (33%) and diagnostic and therapeutic professionals (10%). Physicians and administrative staff accounted for 8% each. The most frequently reported source of infection was occupational (43%), owing to worker-to-worker transmission (45%) and patient-to-worker transmission (36%). The most frequent moments of infection perceived corresponded to the removal of protective equipment during meals and moments of rest in the staff and changing rooms. The study revealed that occupational transmission from patients and colleagues might be an important source of SARS-CoV-2 infection in healthcare workers. Spread between colleagues accounted for 45% of the occupational source infections reported. Implementing physical distancing measures and limiting the number of people in changing and rest rooms could significantly reduce infection and related absenteeism.


Next-generation AAV vectors-do not judge a virus (only) by its cover.
Recombinant adeno-associated viruses (AAV) are under intensive investigation in numerous clinical trials after they have emerged as a highly promising vector for human gene therapy. Best exemplifying their power and potential is the authorization of three gene therapy products based on wild-type AAV serotypes, comprising Glybera (AAV1), Luxturna (AAV2) and, most recently, Zolgensma (AAV9). Nonetheless, it has also become evident that the current AAV vector generation will require improvements in transduction potency, antibody evasion and cell/tissue specificity to allow the use of lower and safer vector doses. To this end, others and we devoted substantial previous research to the implementation and application of key technologies for engineering of next-generation viral capsids in a high-throughput 'top-down' or (semi-)rational 'bottom-up' approach. Here, we describe a set of recent complementary strategies to enhance features of AAV vectors that act on the level of the recombinant cargo. As examples that illustrate the innovative and synergistic concepts that have been reported lately, we highlight (i) novel synthetic enhancers/promoters that provide an unprecedented degree of AAV tissue specificity, (ii) pioneering genetic circuit designs that harness biological (microRNAs) or physical (light) triggers as regulators of AAV gene expression and (iii) new insights into the role of AAV DNA structures on vector genome stability, integrity and functionality. Combined with ongoing capsid engineering and selection efforts, these and other state-of-the-art innovations and investigations promise to accelerate the arrival of the next generation of AAV vectors and to solidify the unique role of this exciting virus in human gene therapy.


Effect of PCR template concentration on the composition and distribution of total community 16S rDNA clone libraries.
Total DNA from sediment samples was isolated by a direct lysis technique. Purified DNA was used as template either undiluted or diluted 1:10 prior to polymerase chain reaction (PCR) amplification of 16S rRNA genes. Full-length inserts were analysed for restriction fragment length polymorphisms (RFLP) with the enzyme Cfo1, and the resulting distribution and abundance of RFLP patterns compared between the undiluted and diluted PCR reactions. Results indicate that for low PCR template concentrations, in the range from a few picograms to tens of picograms DNA, proportional representation of specific RFLP types was not reproducible upon template dilution, confirming that PCR amplification of 16S rDNA cannot be used directly to infer microbial abundance. In particular, only 15-24% of the RFLP types recovered from a sample were present in both the undiluted and diluted extracts. We propose that very low template concentrations in the PCR generate random fluctuations in priming efficiency, which led to the contrast in RFLP types observed in the libraries from the undiluted and diluted extracts.


Adenosine-rich extract of Ganoderma lucidum: A safe and effective lipid-lowering substance.
Ganoderma lucidum is a traditional Chinese medicine with a variety of active compounds and possesses adequate lipid-lowering and anti-atherosclerotic effects. However, its main active components and potential mechanisms still remain unclear. Here, we evaluated the anti-hyperlipidemic effect of the adenosine extract from Ganoderma lucidum (AEGL) in high-fat-diet (HFD)-induced hyperlipidemic ApoE-/- mice and explored the underlying biological mechanism by multi-omics analysis. Treatment with AEGL for 8 weeks significantly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) by 45.59%, 41.22%, and 39.02%, respectively, as well as reduced liver TC and TG by 44.15% and 76.23%, compared with the HFD-only group. We also observed significant amelioration of hepatic steatosis without liver and kidney damage after AEGL treatment. Regulating the expression and acetylation/crotonylation of proteins involved in the PPAR signaling pathway may be one of the potential mechanisms involved in the observed lipid-lowering effects of AEGL.


Association between obesity and heart rate variability indices: an intuition toward cardiac autonomic alteration - a risk of CVD.
Obese people have a higher prevalence of cardiovascular disease, which is supposed to be due to autonomic dysfunction and/or metabolic disorder. The alterations in cardiac autonomic functions bring out the changes in the heart rate variability (HRV) indicators, an assessing tool for cardiac autonomic conditions. To compare the cardiac autonomic activity between obese and normal weight adults and find out the highest association between the indices of HRV and obesity. The study was conducted in 30 adult obese persons (body mass index [BMI] >30 kg/m2) and 29 healthy normal weight controls (BMI 18-24 kg/m2). Short-term HRV variables were assessed using standard protocol. Data were compared between groups using Mann-Whitney U test. Obesity indices such as waist circumference, hip circumference, waist-hip ratio (WHR), and BMI were measured and calculated, and they were correlated with HRV indices using Spearman's correlation analysis. In the obese group, there was a significant increase in the mean heart rate, whereas the HRV parasympathetic indicators were less (eg, root mean square of differences of successive RR intervals [28.75 {16.72-38.35} vs 41.55 {30.6-56.75} ms, p=0.018], number of RR intervals that differ by >50 ms, that is, NN50 [15.5 {2-39} vs 83.5 {32.75-116.25}, p=0.010], etc) and the sympathetic indicator low frequency (LF)/high frequency (HF) ratio (1.2 [0.65-2.20] vs 0.79 [0.5-1.02], p=0.045) was more than that of the normal weight group. Spearman's correlation between HRV and obesity indices showed significant positive correlation of WHR with LF in normalized unit (r=0.478, p<0.01) and LF/HF ratio (r=0.479, p<0.01), whereas it had significant negative correlation with high frequency power ms2 (r=-0.374, p<0.05) and HF in normalized unit (r=-0.478, p<0.01). There was a nonsignificant correlation of BMI with HRV variables in obese individuals. Increased WHR, by far an indicator of visceral adiposity, was strongly associated with reduced cardiac parasympathetic and increased sympathetic activity in obese individuals defined by BMI. However, BMI itself has a weak relationship with HRV cardiac autonomic markers. Thus, even with a slight increase in WHR in an individual, there could be a greater risk of cardiovascular morbidity and mortality brought about by cardiac autonomic alterations.


Single-beam, dual-view digital holographic interferometry for biomechanical strain measurements of biological objects.
We describe a method for dual-view biomechanical strain measurements of highly asymmetrical biological objects, like teeth or bones. By using a spherical mirror, we were able to simultaneously record a digital hologram of the object itself and the mirror image of its (otherwise invisible) rear side. A single laser beam was sufficient to illuminate both sides of the object, and to provide a reference beam. As a result, the system was mechanically very stable, enabling long exposure times (up to 2 min) without the need for vibration isolation. The setup is simple to construct and adjust, and can be used to interferometrically observe any object that is smaller than the mirror diameter. Parallel data processing on a CUDA-enabled (compute unified device architecture) graphics card was used to reconstruct digital holograms and to further correct image distortion. We used the setup to measure the deformation of a tooth due to mastication forces. The finite-element method was used to compare experimental results and theoretical predictions.


Kinetics of reduction of ferrylmyoglobin by (-)-epigallocatechin gallate and green tea extract.
The hypervalent heme pigment ferrylmyoglobin, a potential prooxidant in muscle tissue and meat, is efficiently reduced by epigallocatechin gallate (EGCG) from green tea and by green tea polyphenol extract (GTP) in neutral or moderately acidic aqueous solution (0.16 M NaCl) to yield metmyoglobin in two parallel processes. The second-order rate constant for direct reduction at pH 7.4 and 25 degrees C was found to have the value 1170 +/- 83 M(-1).s(-1) and activation parameters DeltaH(#) = 70.6 +/- 7.2 kJ.mol(-1) and DeltaS(#) = 50.7 +/- 24.1 J.mol(-1).K(-1) for EGCG and the value 2300 +/- 77 M(-1).s(-1) and parameters DeltaH(#) = 60.6 +/- 2.6 kJ.mol(-1) and DeltaS(#) = 23 +/- 9 J.mol(-1).K(-1) for GTP (based on EGCG concentration). For decreasing pH, the rate increased moderately due to a parallel reduction of protonated ferrylmyoglobin. At physiological pH, EGCG is more efficient in deactivating ferrylmyoglobin than other plant phenols investigated, and the relatively high enthalpy and positive entropy of activation suggest an outer-sphere electron transfer mechanism. The interaction between EGCG and other tea catechins in GTP could be responsible for the even stronger ability for GTP to deactivate ferrylmyoglobin.


Carotid stenting.
Carotid angioplasty and stenting (CAS) has developed as an alternative for carotid endarterectomy (CEA) for the treatment of carotid artery disease. As technology has improved, procedural risks have declined and are approaching those reported for CEA. The benefits and durability of CAS compared with CEA are still being studied in ongoing randomised controlled trials. This review discusses the evolution of techniques and materials and the results of randomised trials and observational studies.


Characteristics of psychotic disorder due to traumatic brain injury: an analysis of case studies in the literature.
The authors analyzed data from 69 published case studies of Psychotic Disorder Due to Traumatic Brain Injury (PDTBI) in order to describe its common characteristics and assist in its diagnosis and differentiation from schizophrenia. The majority of these PDTBI patients were males with onset of symptoms occurring within the first 2 years after moderate to severe head injury. A majority showed abnormalities on MRI/CT and EEG with localization in the frontal and temporal areas. The general presentation included delusions and hallucinations without co-occurring negative symptoms. The findings demonstrate that patients with PDTBI have a profile that distinguishes itself from schizophrenia.


Ingested cylindrical batteries in an incarcerated male: a caustic tale!
A 37-year-old incarcerated man presented to the accident and emergency department following the deliberate ingestion of eight cylindrical batteries. He also admitted to inserting a razor blade wrapped in cling-film into his rectum; in addition, he sustained a self-inflicted laceration to his left antecubital fossa, using the metal casing from a battery. His medical history included a borderline and emotionally unstable personality disorder. He had ingested several batteries 12 months previously and required an emergency laparotomy to retrieve them. On the present admission, as there was no clinical evidence of small bowel obstruction, he was treated conservatively with serial radiographs. Following conservative management, the batteries failed to progress through the gastrointestinal tract, hence a laparotomy was performed and all the batteries were extricated. This paper discusses the management and associated sequelae of patients presenting following the intentional ingestion of a battery.


The complete amino acid sequence and disulphide bond arrangement of oat alcohol-soluble avenin-3.
We have elucidated the complete amino acid sequence of one of the avenin components, avenin-3, isolated from oat (Avena sativa L.), variety Narymsky 943. The sequence of the protein was determined by sequencing of CNBr and trypsin-generated peptides in combination with mass spectrometry. The protein is a single polypeptide chain, consisting of 201 amino acid residues with M(r) 23,252.8. The N-terminal amino acid residue of the protein is blocked with 5-oxoproline (pyroglutamic acid). All eight cysteine residues in avenin-3 are involved in disulphide bonds. The positions of these bonds were established by identification of a CNBr cleavage product of the intact avenin containing all the disulfide bonds (S-S core). Subsequent subdigestion of this S-S core allowed isolation of disulphide bonded peptides detected by differential reverse-phase HPLC before and after reduction. As a result, all four disulphides Cys50 Cys183, Cys58 Cys77, Cys84 Cys85 and Cys97 Cys191 were identified. Comparison of avenins with other prolamins demonstrates a high degree of similarity, which is especially pronounced around the cysteine residues. Avenins differ slightly from other prolamins in having unique N-terminal sequences and some differences in the repeated sequence motifs.


Simultaneous integrated boost (SIB) for treatment of gynecologic carcinoma: Intensity-modulated radiation therapy (IMRT) vs volumetric-modulated arc therapy (VMAT) radiotherapy.
The aim of this study was to quantitatively compare dosimetric criteria between intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans for patients undergoing radiation treatment of gynecologic carcinoma with a simultaneous integrated boost (SIB) technique. IMRT and VMAT plans were retrospectively analyzed for 20 patients. The elective volume was planned to receive 45 Gy in 25 fractions of 1.8 Gy, with the integrated boost volume (involved nodes) receiving 55 Gy simultaneously. The same dose constraints were employed during the optimization of both techniques. IMRT plans consisted of 9 to 11 fields at equally spaced gantry angles. VMAT plans consisted of 3 full arcs of 360°. A large variety of dose metrics across planning target volume (PTV)45, PTV55, bladder, rectum, sigmoid, bowel, kidneys, and femoral heads were extracted per patient, per plan. Conformity and homogeneity indices were also calculated and compared for each target volume. The total number of monitor units as well as the integral dose was also compared between IMRT and VMAT. The Wilcoxon signed rank test was performed to evaluate any significant differences between parameters, with an applied Bonferroni correction to account for multiple testing (significance level, p < 0.0006). The results demonstrate the equivalence of the 2 planning techniques across all studied parameters, with the exception of the expected decrease in monitor units that VMAT is capable of achieving. The findings of this study suggest that IMRT and VMAT are both acceptable options for applying simultaneous integrated boost techniques for the treatment of gynecologic cancers. The technique of choice will be dependent on departmental resources and should be considered on a case-by-case basis.


[Measuring work-related physical demand: factorial structure and reliability of items on posture, handling of loads and repetitiveness].
This study sought to analyze the dimensionality of a set of items that measure work-related physical demand, their internal consistency and their test-retest reliability. We carried out an exploratory factorial analysis of ten physical demand items in two populations, totaling 1,070 workers from the footwear industry and from urban cleaning, using weighted least squares means and adjusted variance with Promax oblique rotation. We measure internal consistency using Cronbach's alpha. The test-retest used a subsample of 121 workers, using quadratic weighted kappa. We identified two dimensions in urban cleaning and three in the footwear industry: (1) dynamic work with anomalous postures; (2) work that requires handling material; and (3) work that demands repetitive motions. Reliability was excellent for upright work posture, good for walking, moderate for lifting loads, squatting, rotated trunk and only regular for repetitive motions and arms above shoulders. The dimensions we identified through factorial analysis are compatible with the physical demands of urban cleaning and the footwear industry and, in general, showed good internal consistency. The 10 items' reliability was compatible with the literature, showing excellent to good reliability for general posture, moderate for specific body segment posture and regular for repetitiveness. Results reveal the specificity of each occupational group, which suggests a dimensionality of physical demand items, supporting their use for measuring physical exposure.


Cell counting and carbon utilization velocities via microbial calorimetry.
Bacteria rapidly metabolize sugars and produce heat accordingly (Escherichia coli, aerobic conditions, 25 degrees C). Two kinds of heat output are gotten: (1) from excess cells and limiting carbon, 2 x 10(9) to 5 x 10(9) cells, 5-50 nanomole glucose; (2) from limited cells and excess carbon, 0. 1 x 10(9)-1 x 10(9) bacteria and 200-600 nmol glucose. The thermograms from heat conduction calorimetry under the first conditions measure velocities of sugar uptake and initial metabolic throughput in 1-6-min time spans before a growth cycle possibly can occur. Under the second conditions with limited cells, power output plateaus to a steady state proportional to cell biomass and number of cells. In order to evaluate the calorimetric means for measuring number of cells, six independent means including spectrophotometry (turbidity) were compared: microkjeldahl nitrogen, biuret protein, dry weight, microscopy direct counting in Petroff-Hausser chambers, and viable colony counting. Using turbidity as a central standard, all methods including calorimetry under the second set of conditions agree within +/-18% of one another. Spectrophotometry is the most rapid method but is seriously interfered with by pigments that absorb and foreign particles that also scatter. Calorimetry requires 10-30 min but measures cell numbers in opaque samples impossible for optical means.


Reduced cocaine self-administration in muscarinic M5 acetylcholine receptor-deficient mice.
The reinforcing effects of cocaine have been related to increased extracellular concentrations of dopamine in the ventral striatum. Several studies suggest that M5 muscarinic receptors facilitate striatal dopamine release. We tested the hypothesis that the reinforcing effects of cocaine are decreased in M5 receptor-deficient mice using chronic intravenous cocaine self-administration in extensively backcrossed mice. We also assessed whether operant performance generally, rather than cocaine self-administration specifically, was altered in the mutant mice. To this end, we evaluated both food-maintained operant behavior and cocaine self-administration under a fixed ratio 1 and a progressive ratio (PR) schedule of reinforcement. We also evaluated acquisition of self-administration in experimentally naive mice using several doses of cocaine. M5 receptor deletion decreased self-administration of low to moderate doses of cocaine under a PR schedule of reinforcement and diminished acquisition of self-administration of a low dose in experimentally naive mice. We found no differences between genotypes in food-maintained behavior. The present study extends our previous findings using backcrossed mice and covering various experimental conditions. Our results indicate that M5 receptor deletion diminished the reinforcing effects of low doses of cocaine and identified specific conditions under which this may be observed.


Blessings: the influence of a spirituality-based intervention on psychospiritual outcomes in a cardiac population.
Cardiovascular disease affects an individual's body, mind, and spirit. The multidimensional impact of heart disease requires holistic care that includes the spiritual dimension for patients to achieve optimal healing and recovery. This pretest, posttest repeated-measures quasi-experimental study sought to examine the influence of a spiritual intervention on psychospiritual outcomes in a cardiac population.


Characterization of NADP+ binding to perdeuterated MurB: backbone atom NMR assignments and chemical-shift changes.
Backbone-atom resonances have been assigned for both the substrate-free and the NADP+-complexed forms of UDP-N-acetylenolpyruvylglucosamine reductase (MurB), a monomeric, 347-residue (38.5 kDa) flavoenzyme essential for bacterial cell-wall biosynthesis. NMR studies were performed using perdeuterated, uniformly 13C/15N-labeled samples of MurB. In the case of substrate-free MurB, one or more backbone atoms have been assigned for 334 residues (96%). The assigned backbone atoms include 309 1HN and 15N atoms (94%), 315 13CO atoms (91%), 331 13C(alpha) atoms (95%), and 297 13C(beta) atoms (93%). For NADP+-complexed MurB, one or more backbone atoms have been assigned for 313 residues (90%); these include 283 1HN and 15N atoms (86%), 305 13CO atoms (88%), 310 13C(alpha) atoms (89%), and 269 13C(beta) atoms (84%). The strategies used for obtaining resonance assignments are described in detail. Information on the secondary structure in solution for both the substrate-free and NADP+-complexed forms of the enzyme has been derived both from 13C(alpha) and 13C(beta) chemical-shift deviations from random-coil values and from 1HN-1HN NOEs. These data are compared to X-ray crystallographic structures of substrate-free MurB and MurB complexed with the UDP-N-acetylglucosamine enolpyruvate (UNAGEP) substrate. NADP+ binding induces significant chemical-shift changes in residues both within the known UNAGEP and FAD binding pockets and within regions known to undergo conformational changes upon UNAGEP binding. The NMR data indicate that NADP+ and UNAGEP utilize the same binding pocket and, furthermore, that the binding of NADP+ induces structural changes in MurB. Finally, many of the residues within the UNAGEP/NADP+ binding pocket were difficult to assign due to dynamic processes which weaken and/or broaden the respective resonances. Overall, our results are consistent with MurB having a flexible active site.


Estimating marginal causal effects in a secondary analysis of case-control data.
When an initial case-control study is performed, data can be used in a secondary analysis to evaluate the effect of the case-defining event on later outcomes. In this paper, we study the example in which the role of the event is changed from a response variable to a treatment of interest. If the aim is to estimate marginal effects, such as average effects in the population, the sampling scheme needs to be adjusted for. We study estimators of the average effect of the treatment in a secondary analysis of matched and unmatched case-control data where the probability of being a case is known. For a general class of estimators, we show the components of the bias resulting from ignoring the sampling scheme and demonstrate a design-weighted matching estimator of the average causal effect. In simulations, the finite sample properties of the design-weighted matching estimator are studied. Using a Swedish diabetes incidence register with a matched case-control design, we study the effect of childhood onset diabetes on the use of antidepressant medication as an adult. Copyright © 2017 John Wiley & Sons, Ltd.